FDA approval to move forward with Phase I safety trial using Schwann cells in SCI

The Miami Project to Cure Paralysis, a Center of Excellence at the University of Miami Miller School of Medicine, has received permission from the Food and Drug Administration to begin a Phase 1 clinical trial to evaluate the safety of transplanting human Schwann cells to treat patients with recent spinal cord injuries.

We are not recruiting anybody until we obtain approval from our Institutional Review Board.

This trial is just 1 brick in the wall. We will continue working with our scientific colleagues to test other “bricks” in the wall to ultimately develop a strong defense to prevent or reverse the many effects of paralysis.

The approval to move forward with this trial should represent hope for all people living with SCI. There are so many scientists dedicated to developing safe and effective treatments for SCI; we at the Miami Project are but a few. We are all determined, however, to collaborate and move promising treatments forward in a safe and effective manner to ultimately benefit everyone with SCI.

What is a brief overview of the trial?
A potential subject would have to agree to participate within 5 days after his/her injury, which is considered the acute phase. At that point, he/she would have a biopsy of a nerve in one leg to obtain his or her own Schwann cells. The Schwann cells then need to grow in a culturing facility for 3 to 5 weeks to multiply in number and undergo purification. By the time the Schwann cells are actually transplanted into the site of spinal cord injury, the participant would actually be 26-40 days post-injury, which is considered the sub-acute phase.

All procedures would be conducted in Miami at The Miami Project, the University of Miami Hospital, and at Jackson Memorial Hospital. We will be following participants for 1 year after the transplantation surgery and evaluating their neurologic status, medical status, pain symptoms, and muscle spasticity very closely.

What is the goal of the clinical trial?
Safety. The goal of every phase I clinical trial is to demonstrate safety. We have designed a clinical trial that will minimize risk and maximize evaluation of safety.

Is this a cure for paralysis?
No.

The spinal cord is a very complex organ, after all it, in combination with the brain, controls every single aspect of our body. Hence, when the spinal cord sustains damage people lose more than just the ability to walk. Aside from the loss of movement and sensation, almost every single SCI results in the loss of bladder and bowel control. Depending on where in the spinal cord the injury occurs, there may be additional impairments in sexual function, loss of the ability to regulate body temperature and blood pressure, reduced breathing and coughing capacity, and inefficient metabolism of food.

Inside the spinal cord, there is a multitude of damage. First, there is primary damage. In regard to traumatic injury, the primary damage is a direct result of the impact of whatever caused the injury (ex. fall, gunshot, car crash, etc.). Second, waves of biological events are triggered by the primary damage that ends up causing secondary damage. The main contributor to the secondary damage is the immune system. The end result is that spinal cord tissue that was not damaged by the primary impact ends up dying. Third, cells die in and around the injury site. These include motor nerve cells (motoneurons), sensory nerve cells (sensory neurons), relay nerve cells (interneurons), and multiple types of support cells called “glia” (astrocytes, oligodendrocytes). Fourth, individual nerve fibers (axons) running up and down the spinal cord get severed. The cell bodies of these severed axons are located away from the injury site and often remain alive; however, they can no longer communicate. Fifth, inhibitory scar tissue develops around the injured area.

So, it does not make sense then, to expect one intervention to be able to repair all the different types of damage that occur and restore all of the different functions that are impaired. Schwann cells are one component of a multi-faceted cure.

What age groups are included in the trial?
18-50 years old at the time of spinal cord injury

What injury levels are included in the trial?
T3 to T11, ASIA Impairment Scale grade A

Will the trial need to include both men and women, or the first 8 who meet the criteria and consent?
Men and women will be eligible for the trial, however, the first 8 people who meet all of the inclusion criteria, agree to participate, and undergo transplantation of their Schwann cells will be the participants.

Will the people included in this trial be able to receive hypothermia?
No, that would confound the interpretation of the results of this trial.

What do we hope to learn from this study?
Safety. First, we hope to demonstrate that we can insert a needle into the center of the spinal cord injury site without causing any damage. Second, we hope to demonstrate that transplanting one’s own Schwann cells into the thoracic cord does not cause additional damage.

How long will it take to complete this trial?
It could take 2-3 years from the time we enroll the first subject until the final subject is 1 year post-transplantation.

Why does it take so long to complete the trial?
There are many reasons. 1) Only about 25% of all spinal cord injuries are between T3-T11 and, of those, many sustain additional trauma during the accident, which will exclude them from this particular trial. 2) For the first 2 subjects, there is a 1 month waiting period between the time of transplantation surgery and enrollment of the next subject; this leads to about 2 ½ – 3 months between enrollments. Realistically, it could take 7 ½ – 9 months to enroll and transplant the first 3 subjects in the trial. After that, we can enroll 1 subject each month. So, best case scenario, it could take 12 – 15 months to get all 8 subjects enrolled and transplanted. 3) Each subject will be followed for 1 year following the transplantation procedure to analyze safety. Therefore, it could take 2 – 2 ½ years from enrolling the first subject to collecting the final data from the last subject. The data will then need to be analyzed and submitted to the FDA.

In light of Geron shutting down their trial, what are the guarantees that the same will not happen to this trial?
The Miami Project is committed to moving basic science discoveries forward into clinical trials for people living with spinal cord injury. Being based within an academic institution, the University of Miami Miller School of Medicine, we are driven by factors different from corporations in the business world. Our goal is to translate safe, promising discoveries to clinical trials where they can be thoroughly evaluated and ultimately approved by the FDA for medical use.

Why does this trial include only acutely injured people?
The main reason we are doing new injuries first is because we had more animal data in that setting and it allowed us to seek FDA approval faster. Getting faster FDA approval means going into people faster, which means finding out about human safety faster.

Will the trial eventually include chronically injured people?
This specific clinical trial will not include chronically injured people. We are currently conducting more animal chronic transplantation preclinical studies and we will soon being a combined exercise and locomotor rehabilitation study for chronically injured people to determine the minimum exercise and rehabilitation needed to prepare people for transplantation surgery and to ensure that they are neurologically stable. We will take all of that data and design another clinical trial specifically for people with a chronic injury. We will submit that in addition to safety data generated by the acute trial to the FDA for approval.

How can I get my loved one in this trial?
First, we are actively seeking ethical approval by the University of Miami Institutional Review Board. Once we receive that we will begin recruitment for the trial.

If you have a loved one who has had a thoracic spinal cord injury less than 5 days ago, call the Miami Project Education Department at 305-243-7108 for information and preliminary screening.

If you or your loved one has a spinal cord injury that is more than 5 days old, we recommend staying healthy, being active, and participating in the studies that are currently approved, such as exercise, rehabilitation, spasticity, pain, etc.

Think of this as our building block to developing the most effective treatments for people living with SCI. The best way for anyone to get access to these treatments fastest is to keep healthy and in very good condition so that he/she can qualify for clinical trials as they become available. For treatments to go all the way through multiple clinical trials and become mainstream medical practice in the “clinic”, it could take 10-15 years or more depending on the intervention being tested. Participating in clinical trials not only helps us move the field forward faster, but may also benefit the clinical trial participants faster than waiting.